Un/met: a mixed-methods study on primary healthcare needs of the poorest population in Khyber Pakhtunkhwa province, Pakistan.

BACKGROUND: Access of all people to the healthcare they need, without financial hardship is the goal of Universal Health Coverage (UHC). As UHC initiatives expand, assessing the needs of vulnerable populations can reveal gaps in the system which may be covered by relevant policies. In this study we (i) identify the met and unmet primary healthcare needs of the poorest population of Khyber Pakhtunkhwa province (KP), Pakistan, and (ii) explore why the gaps exist. METHODS: We used Leveque's Framework of Patient-centred Access to Healthcare to examine unmet primary healthcare (PHC) needs and their underlying causes for the poorest population in four districts of Khyber Pakhtunkhwa province, Pakistan. Using a triangulation mixed methods design, we analysed data from a quantitative household survey of744 households, 17 focus group discussions with household members and, 11 interviews with healthcare providers. RESULTS: Our results show that indicate that despite service utilization, PHC needs were not met, primarily due to prohibitively high costs at each stage of access. Furthermore, gaps in outreach and information (approachability), and varying availability of medicines and diagnostics at facilities (appropriateness) the supply side as well as difficulties in navigating the system (inability to perceive) and adhering to prescriptions (inability to engage) on the demand side, also led to unmet PHC needs. Going beyond utilization, our findings highlight that engagement with care is an important determinant of met needs for vulnerable populations. CONCLUSION: Social health protection policies can contribute to advancing UHC for primary care. However, in our setting, enhancing communication and outreach, addressing gender and age disparities, and improving quality of care and health infrastructure are necessary to fully meet the needs of the poorest populations.

Smokeless Tobacco Cessation Support in Dental Hospitals in Pakistan: Dentists and Dental Patients' Perspectives on Current Practices, Support Needed, and Opportunities Available.

INTRODUCTION: Despite evidence on the effectiveness of tobacco cessation interventions in dental settings, the implementation remains low, especially for smokeless tobacco (ST). The purpose of this study was to develop an understanding of the influences governing the implementation of ST cessation support in dental hospitals. AIMS AND METHODS: A multicenter qualitative study was conducted at two tertiary-care dental hospitals, in Pakistan. Semi-structured interview guide, guided by the Capability-Opportunity-Motivation-Behavior (COM-B) model, were used to capture the views of dentists (n = 12) and dental patients (n = 12), regarding ST cessation support in dental hospitals. Framework approach was used to thematically analyze the data. RESULTS: Screening of ST users in routine dental practice was seldom practiced and the cessation support offered was brief advice. Barriers identified by dentists included: Fear of offending and stereotyping patients; lack of knowledge and skills; lack of privacy; lack of belief in the effectiveness of behavioral support; lack of time and workload pressure; ST use amongst dentists; lack of referral systems and; the absence of a mandatory requirement of offering ST cessation support. Facilitators included: Delivering support through junior dentists and the length of interaction between the dentist and the patient. Naswar was the most common ST product used by dental patients. Patients reported receiving negligible cessation support from any healthcare provider. CONCLUSIONS: A range of influences governing the implementation of ST cessation support in dental hospitals were identified. These findings can inform the implementation of behavioral interventions for ST cessation in dental and other clinical settings, in low and middle-income countries. IMPLICATIONS: Smokeless tobacco control considerably lags, in comparison to the control of combustible tobacco. This is the first study that qualitatively explores the implementation of ST cessation support in dental settings in Pakistan. Utilizing the "Capability-Opportunity-Motivation-Behavior" model, it provides an in-depth understanding of the inability of dentists in implementing effective behavioral interventions for ST cessation support in routine dental practice. Highlighting the striking discrepancy between the patient's need for and receptivity towards cessation support and the dentists' concerns over their patients' receptivity towards cessation support, it calls for the need for effective implementation strategies to optimize dentist-led tobacco cessation interventions in low-resource settings.

The Lifetime Health and Economic Burden of Smokeless Tobacco use in Bangladesh, India, and Pakistan: Results From ASTRAMOD.

INTRODUCTION: Under the current policy landscapes, the lifetime health and economic burden of smokeless tobacco (ST) products, consumed by over 297 million ST users in South Asia, is unknown. The aim of this study was to estimate the lifetime health effects and costs attributable to current and future ST use in Bangladesh, India, and Pakistan where the majority of ST users live. AIMS AND METHODS: We developed a Markov-based state-transition model (ASTRAMOD) to predict the lifetime costs of treatment of four diseases (oral, pharyngeal, esophageal cancers, and stroke) and disability-adjusted life years (DALYs), attributable to the current and future use of ST under existing ST policy scenario. Country-specific Global Adult Tobacco Surveys, life tables, and meta-analyses of South Asian and South East Asian studies were used to populate the model. A probabilistic sensitivity analysis evaluated the uncertainty in model predictions. RESULTS: If there were no change in the current ST policies, the lifetime ST-attributable treatment costs would be over US$19 billion in India, over US$1.5 billion in Bangladesh, and over US$3 billion in Pakistan. For all countries, the attributable costs are higher for younger cohorts with costs declining with increasing age for those over 50. The model predicted that a typical 15-year-old male adoloscent would gain 0.07-0.18 life years, avert 0.07-0.19 DALYs, and generate a cost-savings of US$7-21 on healthcare spending if ST policies were changed to eliminate ST use. CONCLUSIONS: Policy interventions aimed at decreasing the uptake of ST and increasing quitting success have the potential to substantially decrease the economic and health burden of ST. IMPLICATIONS: This study provides the most comprehensive estimates of the lifetime health and economic burden of ST by 5-year age and sex cohorts. This is also the first study that highlights the scale of health and economic burden of ST in Bangladesh, India, and Pakistan if there were no changes in the current ST policies. Policymakers and practitioners can use the reported data to justify their decisions to improve current ST policies and practices in their country. Researchers can use the ASTRAMOD methodology to estimate the impact of future ST policy changes.

A Systematic Investigation of Tobacco Industry Sourced Data Relating to Illicit Tobacco Trade Featured in Pakistan's Media Coverage (2015-2020).

INTRODUCTION: Previous evidence suggests the tobacco industry uses media to disseminate misleading narratives relating to illicit tobacco trade (ITT) as part of efforts to influence policy outcomes. Such evidence is largely high-income countries (HIC) focused, resulting in a literature gap for low- and middle-income countries (LMICs). Pakistan and its annual budget cycle are used as a case study for addressing this gap. AIMS AND METHODS: Electronic English-language articles from newspapers in Pakistan (328) were sourced from LexisNexis and a sub-sample of Urdu-language electronic articles (12) were identified through internet searches. The articles were published between 2015 and 2020 and included claims/estimates relating to ITT, which were coded to identify cited data sources. Changes in media coverage before and after Pakistan's annual budget announcements were explored via Wilcoxon signed rank and Poisson regression tests. RESULTS: Of the 357 claims/estimates analyzed, 66 (20%) were industry-funded. The most prevalent sources were national government bodies (36.6%) and tobacco companies or their representatives (15.1%). Wilcoxon signed-rank and Poisson regression tests on the frequency of English-language articles both created a p-value of < .05 for the frequency of relevant articles between the months of April and May, compared to the other months, indicating statistical significance. CONCLUSIONS: There was a statistically significant increase in the number of English-language articles featuring claims/estimates relating to Pakistan's ITT in the months leading up to the annual budget each year. The government should consider measures to improve transparency standards within media coverage and promote factcheck journalism to safeguard against industry tactics to manipulate public discourses. IMPLICATIONS: This paper is, to the best of our knowledge, the largest exploration of the use of data sourced from the tobacco industry within a country's media that has been undertaken to date, utilizing a team of seven coders across the United Kingdom and Pakistan. Our findings reveal weaknesses within media coverage of ITT in Pakistan, both in English and Urdu language publications. We encourage the government to consider new standards to enhance transparency and promote factcheck journalism within media coverage in the country.

Process evaluation of a pragmatic feasibility trial on smokeless tobacco cessation intervention delivered in dental hospitals.

BACKGROUND: Article 14 of the WHO 'Framework Convention on Tobacco Control' recommends, that all oral healthcare providers provide support for tobacco cessation, to all patients. Despite evidence on the effectiveness of tobacco cessation interventions in dental settings, implementation remains low in most high-burden countries like Pakistan. A pragmatic pilot trial of a dentist-delivered behavioural support intervention for smokeless tobacco (ST) cessation, was conducted in dental hospitals in Pakistan. This paper presents the findings of the process evaluation of the trial. METHODS: A mixed-method process evaluation of a multi-centre randomised control pilot trial of dentist-delivered behavioural support intervention ST cessation was conducted. The intervention included three sessions namely: pre-quit, quit and post-quit sessions. The process evaluation involved: semi-structured interviews with trial participants (n = 26, of which dental patients were n = 13 and participating dentists were n = 13 conducted from June-August 2022); and fidelity assessment of audio recordings of the intervention sessions (n = 29). The framework approach was used to thematically analyse the interview data. RESULTS: Overall the trial procedures were well accepted, however, young patients expressed uneasiness over revealing their ST use status. The intervention was received positively by dentists and patients. Dentists identified some challenges in delivering behavioural support to their patients. Of these, some were related to the contents of the intervention whereas, others were related to the logistics of delivering the intervention in a clinical setting (such as workload and space). Acceptability of the intervention resources was overall low amongst young patients as they did not take the intervention resources home due to fear of their family members finding out about their ST use. The intervention was successful in achieving the intended impact (in those who engaged with the intervention), i.e., change in the patients' ST use behaviour. Giving up ST with the aid of behavioural support also had an unintended negative effect i.e., the use of harmful substances (cannabis, cigarettes) to give up ST use. Patients' satisfaction with their dental treatment seemed to influence the intervention outcome. CONCLUSION: While there are many variables to consider, but for the participants of this study, behavioural support for abstinence delivered through dentists during routine dental care, appears to be an acceptable and practical approach in helping patients give up ST use, in a country like Pakistan, where negligible support is offered to ST users.

Co-application of Parthenium biochar and urea effectively mitigate cadmium toxicity during wheat growth.

Environmental contamination by cadmium (Cd), a highly toxic heavy metal, poses significant health risks to plants and humans. Biochar has been effectively used to promote plant growth and productivity under Cd stress. This study presents an innovative application of biochar derived from the invasive weed Parthenium hysterophorus to promote plant growth and productivity under Cd stress. Our study includes detailed soil and plant analyses, providing a holistic perspective on how biochar and urea amendments influence soil properties, nutrient availability, and plant physiological responses. To address these, we established seven treatments: the control, Cd alone (5 mg kg-1), biochar alone (5 %), urea alone (3 g kg-1), biochar with Cd, urea with Cd, and a combination of biochar and urea with Cd. Cd stress alone significantly reduced plant growth indicators such as shoot and root length, fresh and dry biomass, chlorophyll content, and grain yield. However, the supplementation of biochar, urea, or their combination significantly increased shoot length (by 48%, 34%, and 65%), root length (by 73%, 46%, and 70%), and fresh shoot biomass (by 4%, 31%, and 4%), respectively. This improvement is attributed to enhanced soil properties and improved nutrient absorption. The biochar-urea combination also enhanced Cd tolerance by improving total chlorophyll content by 14 %, 13 %, and 16 % compared to the control, respectively. Similaly, these treatments significantly (p < 0.05) boosted the activity of antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase by 51 %, 30 %, and 51 %, respectively, thereby mitigating oxidative stress as a defensive mechanism. The Cd tolerance was improved by biochar, urea, and their combinations, which reduced Cd content in the shoots (by 60.5 %, 38.9 %, and 51.3 %), roots (by 47.5 %, 23.9 %, and 57.6 %), and grains (by 58.1 %, 30.2 %, and 38.3 %) relative to Cd stress alone, respectively. The synergistic effects of biochar and urea are achieved through improved soil properties, nutrient availability, activating antioxidant defense mechanisms, and minimizing the accumulation of metal ions in plant tissues, thereby enhancing plant defenses against Cd stress. Conclusively, converting invasive Parthenium weed into biochar and combining it with urea offers an environmentally friendly solution to manage its spreading while effectively mitigating Cd stress in crops.

Behaviour Change Intervention for Smokeless Tobacco (ST) Cessation Delivered through Dentists in Dental Settings: A pragmatic pilot trial.

INTRODUCTION: Evidence on smokeless tobacco (ST) cessation interventions is scarce. The South Asian (SA) region which shares more than 90% of the burden of ST use, is grossly underrepresented in research on ST cessation. This study aimed to assess the feasibility of delivering and investigating a behavioural support intervention for ST cessation in dental settings in Pakistan. METHODS: A multi-centre, pilot, 2-armed parallel group, individually randomised control trial, with a 1:1 allocation ratio, was conducted at two dental hospitals. Eligibility criteria included: being a ST user; seeking dental treatment and; not currently accessing cessation support. All participants were provided written self-help, ST cessation material. The intervention group also received a dentist-delivered, bespoke behavioural support intervention for ST cessation developed for users of SA origin. Participants were followed up telephonically at three and six months. Self-reported six month abstinence was verified by salivary cotinine. Analysis was descriptive, with 95% confidence intervals presented where appropriate. RESULTS: 100 participants were successfully recruited from the selected hospitals. Of these 78% continued to engage throughout the study duration and provided primary outcome data, whereas, 63% completed all hospital visits. The outcome measures were successfully collected. Biochemically verified six-month abstinence in the intervention and control group was 10% and 4%. CONCLUSIONS: It was feasible to deliver and evaluate a dentist-delivered behavioural support intervention for ST cessation in Pakistan. The data suggested that the intervention may improve ST quit rates. The findings of this study will be useful in informing the design of future definitive studies. IMPLICATIONS: To our knowledge this is the first pragmatic pilot trial on ST cessation in dental settings in Pakistan and the first trial on dentist-delivered structured behavioural support intervention for ST cessation. It adds to the scarce, trial evidence base on ST cessation interventions. Findings suggest behavioural support intervention for ST cessation may improve quit rates. The trial was conducted in a country with poor ST control measures, where ST products are not taxed, the products are sold openly to and by minors and the users are offered negligible cessation support. The findings may therefore be generalisable to LMICs and particularly South Asian countries, with similar policy backgrounds.

Attitudes of smokers towards tobacco control policies: findings from the Studying Tobacco users of Pakistan (STOP) survey.

BACKGROUND: Public attitude is a political driver in successful implementation of tobacco control policies. We assessed support for a range of tobacco control policies among smokers in Pakistan. METHODS: We conducted a household survey among adult smokers in 10 cities of Pakistan, using a two-stage random sampling strategy to select households and Kish grid method to select one smoker per household. Attitudes were measured using a five-point ordinal scale on four policy statements: a complete ban on tobacco sale within 10 years; raising the legal age to buy tobacco from 18 to 21; increasing tobacco taxes to fund healthcare and a ban on smoking in cars with minors. RESULTS: 6014 participants were interviewed between September 2019 and March 2020. Most participants demonstrated strong support for all policy statements: a ban on smoking in cars with minors (86.5%); a complete ban on tobacco sale within 10 years (82.1%); raising the legal age to buy tobacco (77.9%) and increasing tobacco taxes (68.1%). Smokers' support for tobacco control policies increased with age but decreased with higher educational attainment and heaviness of smoking. CONCLUSIONS: There is strong support among smokers in Pakistan to strengthen tobacco control. Given this, policy-makers should strongly consider strengthening existing national policies on tobacco control.

Awareness, perceptions of and compliance with tobacco control policies among naswar vendors in Khyber Pakhtunkhwa Pakistan.

INTRODUCTION: Regulatory compliance in the retail environment is integral to the success of tobacco control. We assessed compliance among naswar (smokeless tobacco product widely used in South Asia) vendors with tobacco control laws. We also assessed their awareness of tobacco-related harms and policies and perceived effect of policies on their sales. METHODS: We surveyed 286 naswar vendors in three districts of the Khyber Pakhtunkhwa province of Pakistan. We recruited general and specialty vendors from urban and rural areas through multistage cluster sampling. Compliance was measured for promotion, sale to/by minors and tax paid on naswar. We used logistic regression analyses for assessing the association between the outcome variables (awareness of tobacco harms and laws, perceptions about the effect of policies on business and compliance with laws) and their predictors. RESULTS: Most vendors (70%) were aware of tobacco-related harms of naswar. Although educated vendors were more aware of tobacco control policies, the greatest awareness was for a ban on sales to/by minors (21% overall). The majority of vendors (76%) violated this policy (measured by self-report), and violations were more common among rural than urban vendors (OR 2.27, 95% CI 1.05 to 4.96). Most vendors (71%) violated a ban on promotion of naswar. Vendors perceived tax increases and sales ban to/by minors as most detrimental for business. CONCLUSIONS: There was poor awareness and compliance among naswar vendors in Pakistan with tobacco control laws. This study finds potential areas for policy interventions that can reduce urban/rural disparities in implementation of and compliance with tobacco control laws.

Illicit cigarette trade in the cities of Pakistan: comparing findings between the consumer and waste recycle store surveys.

BACKGROUND: Concerns about the magnitude of illicit cigarette trade have prevented the Government of Pakistan from increasing tobacco taxes. We estimated the proportion of illicit cigarettes sold in Pakistani cities. Moreover, we compared two methods for collecting cigarette packs and investigated if the illicit cigarette trade equates to tax evasion. METHOD: We analysed cigarette packs collected from 10 cities of Pakistan using two methods: consumer survey based on a two-stage random sampling strategy to recruit adult smokers and photograph their cigarette packs and waste recycle store survey to purchase used cigarette packs. Cigarettes were considered illicit if any one of the following was absent from their packs: text and pictorial health warning, underage sale prohibition warning, retail price and manufacturer's name. From the consumer survey, we also estimated the proportion of smokers who purchased loose cigarettes (illegal) and packs below the minimum retail price. Taxation officers (n=4) were consulted to assess their level of confidence in judging tax evasion using the above criteria. RESULTS: Out of 2416 cigarette packs in the consumer survey, 454 (17.8%; 95% CI 15.4% to 20.2%) were illicit. Similarly, out of 6213 packs from waste recycle shops, 1046 (16.8%; 95% CI 15.9% to 17.7%) were illicit; the difference was not statistically significant (p=0.473). Among consumers, 29.5% bought loose cigarettes and 13.8% paid less than the minimum retail price. The taxation officers considered the manufacturer's name and retail price on cigarette packs as the most relevant criteria to detect tax evasion. CONCLUSIONS: One in six cigarette packs consumed in Pakistan could be illicit. These figures are far less than those propagated by the tobacco industry. Collecting packs from waste recycle stores is an efficient and valid method to estimate illicit cigarette trade.

Non-compliant packaging and illicit smokeless tobacco in Bangladesh, India and Pakistan: findings of a pack analysis.

INTRODUCTION: Illicit smokeless tobacco (ST) trade has seldom been documented despite ST use in at least 127 countries across the world. Based on non-compliance with packaging regulations, we report the proportion of illicit ST products from samples on sale in Bangladesh, India and Pakistan where 85% of global ST users reside. METHODS: We purchased unique ST products from tobacco sellers in two purposively selected administrative areas (division/district) in each of the three countries. The criteria to determine illicit ST products were based on country-specific legal requirements for ST packaging and labelling. These requirements included: 'market retail price disclosure', 'sale statement disclosure', 'pictorial health warning (PHW) pertinence', 'appropriate textual health warning' and 'using misleading descriptors (MDs)'. Non-compliance with even one of the legal requirements was considered to render the ST product illicit. RESULTS: Almost all ST products bought in Bangladesh and India were non-compliant with the local packaging requirements and hence potentially illicit, all products in Pakistan lacked desirable features. The most common feature missing was health warnings: 84% packs in Bangladesh, 93% in India, and 100% in Pakistan either did not have PHW or their sizes were too small. In Bangladesh, 61% packs carried MDs. In India and Pakistan, the proportions of such packs were 32% and 42%, respectively. CONCLUSIONS: Weak and poorly enforced ST control policies may be slowing the progress of tobacco control in South Asia. Standardised regulations are required for packaging and labelling ST. Improving compliance and reducing sale of cheap illicit products may require business licensing and market surveillance.

Scaling up tobacco cessation within TB programmes: findings from a multi-country, mixed-methods implementation study.

BACKGROUND: Brief behavioural support can effectively help tuberculosis (TB) patients quit smoking and improve their outcomes. In collaboration with TB programmes in Bangladesh, Nepal and Pakistan, we evaluated the implementation and scale-up of cessation support using four strategies: (1) brief tobacco cessation intervention, (2) integration of tobacco cessation within routine training, (3) inclusion of tobacco indicators in routine records and (4) embedding research within TB programmes. METHODS: We used mixed methods of observation, interviews, questionnaires and routine data. We aimed to understand the extent and facilitators of vertical scale-up (institutionalization) within 59 health facility learning sites in Pakistan, 18 in Nepal and 15 in Bangladesh, and horizontal scale-up (increased coverage beyond learning sites). We observed training and surveyed all 169 TB health workers who were trained, in order to measure changes in their confidence in delivering cessation support. Routine TB data from the learning sites were analysed to assess intervention delivery and use of TB forms revised to report smoking status and cessation support provided. A purposive sample of TB health workers, managers and policy-makers were interviewed (Bangladesh n = 12; Nepal n = 13; Pakistan n = 19). Costs of scale-up were estimated using activity-based cost analysis. RESULTS: Routine data indicated that health workers in learning sites asked all TB patients about tobacco use and offered them cessation support. Qualitative data showed use of intervention materials, often with adaptation and partial implementation in busy clinics. Short (1-2 hours) training integrated within existing programmes increased mean confidence in delivering cessation support by 17% (95% CI: 14-20%). A focus on health system changes (reporting, training, supervision) facilitated vertical scale-up. Dissemination of materials beyond learning sites and changes to national reporting forms and training indicated a degree of horizontal scale-up. Embedding research within TB health systems was crucial for horizontal scale-up and required the dynamic use of tactics including alliance-building, engagement in the wider policy process, use of insider researchers and a deep understanding of health system actors and processes. CONCLUSIONS: System-level changes within TB programmes may facilitate routine delivery of cessation support to TB patients. These strategies are inexpensive, and with concerted efforts from TB programmes and donors, tobacco cessation can be institutionalized at scale.

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum.

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.

Supply Chain Actors' Willingness to Switch the Business of Smokeless Tobacco: A Mixed-Methods Study on Naswar Business in Pakistan.

INTRODUCTION: Provision of alternate livelihoods to smokeless tobacco (SLT) supply chain (SC) actors can help in curtailing SLT business and its consumption. We explored the reasons for SC actors' engagement in Naswar (SLT used in South Asia) business and their willingness to switch to other alternatives. AIMS AND METHODS: We conducted an equal-status concurrent mixed-methods study in four districts of Khyber Pakhtunkhwa province of Pakistan. We surveyed 286 general points of sale (GPOS) and exclusive Naswar (EN) vendors through multistage cluster sampling. Additionally, we interviewed 15 tobacco farmers interpretively, being distinct from other SC actors. We assessed the association between vendors' willingness to switch and their awareness about tobacco-harms, profit margin, Naswar as a family business, length of business, education level, and shop type using logistic regression. Qualitative data assessed the farmer's viable alternatives to switch and were analyzed using deductive-inductive thematic analysis. RESULTS: Product demand-77% and profit margins-75% were the main drivers for selling SLT by EN vendors. Half of the GPOS and 25% EN vendors expressed willingness to stop Naswar's sale. Vendors aware of tobacco-harms were more willing to switch, but less likely to switch if Naswar was perceived to bring "good profit." Farmers were mainly cultivating tobacco because of profitability, family-run farm, and perceived land-suitability for tobacco. Lack of government support was main constraint for farmers looking to switch. CONCLUSIONS: A considerable portion of Naswar SC actors in Pakistan are willing to switch to viable alternatives, with profitability of alternatives, support from authorities, and social obligations as key considerations in doing so. IMPLICATIONS: This study highlights that good profit margins in the Naswar business, lack of awareness of tobacco-related health harms, and absence of the government's support are key detriments to switching to alternative businesses among Naswar SC actors in Pakistan. These findings are the first to come out in the context of both Pakistan and Naswar product, making a case for policy interventions focusing on tax increases, awareness campaigns about tobacco-harms, and a proactive role by the government to provide support for the security of livelihoods to those tobacco SC actors who want to switch to other alternatives.

Implementing smokeless tobacco control policy in Pakistan: a qualitative study among Naswar supply chain actors.

OBJECTIVE: To obtain insights into the perceptions of barriers and facilitators to implementation of the WHO Framework Convention on Tobacco Control (FCTC) among smokeless tobacco (SLT) supply chain actors in the Khyber Pakhtunkhwa province of Pakistan. METHODS: We conducted a qualitative study to investigate the perceptions about SLT control policy formulation and implementation among exclusive Naswar sellers and point of sale vendors. We conducted five focus group discussions in three districts of Khyber Pakhtunkhwa using combined deductive-inductive thematic analyses. RESULTS: We identified three central themes that potentially impact policy formulation, its implementation and application. The first theme examines the role of children in the Naswar business: as potential customers, and as potential heirs to a Naswar-selling business. A second theme targets the 'business of Naswar', which includes a specific identity of Naswar sellers, its potential to generate profits and the special case of Naswar regulation as a socially accepted and culturally rooted product. The third theme addresses the unusual ingredients of Naswar and its production process, making Naswar a health risk for consumers and producers. We also report conflicting views regarding SLT control among the supply chain actors. CONCLUSIONS: This study provides insights into the perceptions of important SLT supply-side stakeholders regarding various SLT control policy options based on the FCTC. While there is some opposition to policy approaches like taxation and switching of business, implementing a ban on selling SLT to minors may be a viable option for policymakers in the short term.

Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis.

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-ß signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.

Clinical and functional outcomes following platelet rich plasma in the management of knee osteoarthritis: A case series in a tertiary care hospital.

OBJECTIVE: To clinically assess the efficacy of Platelet rich Plasma (PRP) in improving the functional movement in knee osteoarthritis. METHODS: This prospective case series, on 89 patients, was studied in Sindh Rangers Hospital, Karachi, Pakistan from 1st October 2018 to 31st March 2019. The analysis involved all patients aged 30-65 years diagnosed with grade 1, 2 and 3 arthritis. PRP was administered in three doses one month apart, and patients were evaluated for outcome measures after the third month of the third dose of PRP. To measure functional improvement in knee osteoarthritis, the range of motion (ROM), McMaster University Osteoarthritis index (WOMAC), Western Ontario, and Visual analogue scale (VAS) were used. RESULTS: PRP was infused into 89 patients, with a mean age of 61.24±8.92 years. The average pre-treatment WOMAC score was 37.0 ±2.9, and it was lowered to 18.8± 5.2 after PRP (p<0.02). The pre-treatment VAS was 8.42 ±0.84, and it was reduced to 4.91±2.12, indicating mild to moderate pain. Our PRP therapy was appreciated by 63 (70.07%) patients, while 17 (19.1%) were only partly satisfied. However, 9 (10.1%) patients were dissatisfied. CONCLUSIONS: The results of this case series showed that the use of PRP injections for treating osteoarthritis (grade 1 to 3) proved to be successful in terms of improving functional outcomes and reducing pain intensity.

Mobile Health Augmented Cardiac Rehabilitation (MCard) in Post-Acute Coronary Syndrome Patients: A randomised controlled trial protocol.

OBJECTIVES: To determine the effectiveness of mobile health augmented cardiac rehabilitation (MCard) on health-related quality of life (HRQoL), clinical and behavioural outcomes in post-ACS. METHODS: A single-centre, single-blinded, two-arm randomised controlled trial is planned at Armed Forces Institute of Cardiology (AFIC), Pakistan. The duration was two years, that is from January 2019 till December 2020. A total of 160 participants were recruited and randomly allocated to the control group or the intervention group. Intervention is a mobile health augmented cardiac rehabilitation (MCard), a medically supervised cardiac rehabilitation program for 23-24 weeks. The phase one includes individual counselling during the hospital stay and in phase two includes communication of standardised messages related to healthy lifestyle modification through a specifically designed software. RESULTS: This clinical trial results will give insight into the impact of MCard in improving the health outcomes (HRQoL, clinical and behavioural) of participants. If proven to be effective, this technology can be scaled up and implemented in other cardiac centres in the country. It utilises fewer human resources and can be delivered at a lower cost. CONCLUSION: The study protocol will be giving evidence either MCard can contribute to improving the HRQoL, clinical and behavioural outcomes of post-ACS patients following hospital discharge. Considering the COVID-9 situation, this is the perfect time to implement and evaluate the effectiveness of MCard on health outcomes among post-ACS patients.

Compliance of Oral Snuff (Naswar) Packaging and Sales Practices with National Tobacco Control Laws and the Relevant Articles of Framework Convention on Tobacco Control in Khyber Pakhtunkhwa Pakistan.

INTRODUCTION: Smokeless tobacco (SLT) is a significant contributor to tobacco-related harm in Pakistan but its control has lags behind that of combustible tobacco. We assessed the compliance of Naswar's (a widely used SLT product in the Southeast Asia) packaging and sales practices with the national legislations and relevant articles of the WHO framework convention on tobacco control (FCTC). AIMS AND METHODS: A cross-sectional observational audit was conducted in three districts of Pakistan. We recruited 286 general point of sale (GPOS) and exclusive Naswar sellers (ENS) through a multistage cluster sampling strategy. Data were gathered on packaging and labeling practices of Naswar and advertisement and promotion practices inside and outside the shops. Statistical tests for association between the dependent variable-advertisement practices, and independent variables-area and vendor types were conducted. RESULTS: We analyzed 133 and 49 unique Naswar products sold in 229 GPOS and by 57 ENS, respectively. None of the local products had any written or pictorial health warning. More than half of retailers used one or two methods of advertising Naswar inside the shops while only 9% advertised outside the shops. ENS were more likely to be noncompliant with tobacco advertisement and promotion compared with GPOS. CONCLUSIONS: The study presents first insights on the compliance of Naswar packaging and sale practices with local regulations and WHO FCTC provisions in Pakistan. Almost all products were on display in the shops and none of the local products had any health warning or contents disclosure on the packages. IMPLICATIONS: Naswar is a form of SLT used extensively in Pakistan, Central Asia, and Pashtun populations across the globe. This study provides an important insight into the Naswar retail environment in a geographical setting where the use of Naswar is endemic. The study brings to fore previously unreported issues like an urban-rural disparity, and differences between exclusive and nonENS, with regards to Naswar advertisement and promotion. These findings have potential implication on the implementation of tobacco control retail policies. The lack of health warnings and free display of Naswar brands call for alignment of tobacco control efforts with the FCTC.

Identification of Policy Priorities to Address the Burden of Smokeless Tobacco in Pakistan: A Multimethod Analysis.

INTRODUCTION: We assessed the magnitude of smokeless tobacco (ST) use in Pakistan and identified policy gaps to help ascertain short-, medium-, and long-term priorities. We then elicited stakeholders' views as to which of these identified priorities are most important. METHODS: In a multimethod study, we: analyzed Global Tobacco Surveillance System data sets to estimate ST consumption and disease burden; conducted a documentary review to identify gaps in policies to control ST in comparison with smoking; elicited stakeholders' views in an interactive workshop to identify a set of policy options available to address ST burden in Pakistan; and ranked policy priorities using a postevent survey. RESULTS: Among all tobacco users in Pakistan (n = 24 million), one-third of men and two-thirds of women consume ST. In 2017, its use led to an estimated 18 711 deaths due to cancer and ischemic heart disease. Compared to smoking, policies to control ST lag behind significantly. Priority areas for ST policies included: banning ST sale to and by minors, advocacy campaigns, introduction of licensing, levying taxes on ST, and standardizing ST packaging. A clear commitment to close cooperation between state actors and stakeholder groups is needed to create a climate of support and information for effective policy making. CONCLUSIONS: Smokeless tobacco control in Pakistan should focus on four key policy instruments: legislation, education, fiscal policies, and quit support. More research into the effectiveness of such policies is also needed. IMPLICATIONS: A number of opportunities to improve ST regulation in Pakistan were identified. Among these, immediate priorities include banning ST sale to and by minors, mobilizing advocacy campaign, introduction of licensing through the 1958 Tobacco Vendors Act, levying taxes on ST, and standardizing ST packaging.